Clinical Trial Details
— Status: Active, not recruiting
Administrative data
NCT number |
NCT03403998 |
Other study ID # |
Pro00073078 |
Secondary ID |
|
Status |
Active, not recruiting |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
January 17, 2018 |
Est. completion date |
December 31, 2025 |
Study information
Verified date |
April 2024 |
Source |
University of Alberta |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Musculoskeletal (MSK) pain is a common reason to seek medical treatment. Temporomandibular
disorders (TMDs) are MSK disorders that affect the masticatory muscles, the temporomandibular
joint, and related structures in the neck and head. Current research showed that people with
chronic TMDs have structural and functional brain changes that may contribute to chronic pain
development and maintenance. Therapeutic exercise is a central component in treating chronic
MSK conditions. New therapies, including exercise, appear to have potential in targeting
cortical changes to improve clinical outcomes. However, mechanisms of action are not well
understood, and evidence is limited to a few weak studies and specific populations. Evidence
from our research group highlights neck exercise as potentially useful in treating TMDs.
However, we do not yet know how the brains of women with TMD respond to specific exercise and
whether these changes relate to decreased pain, improved function, and quality of life.
Evidence linking brain plasticity, pain modulation, and exercise therapy is currently
limited, and non-existent for people with TMDs. Objectives: In women with chronic TMD pain,
we will:1) determine the impact of motor control training using visual feedback (MCTF) on
clinical outcomes such as pain intensity and jaw disability, 2) assess the impact of MCTF on
brain structure, using diffusion tensor imaging, 3) assess the impact of MCTF on brain
networks, using resting state functional magnetic resonance imaging, and 4) determine the
effectiveness of MCTF to restore normal muscular structure, performance and fatigability of
neck cervical muscles, using electromyographic analysis. Methods: Women with chronic TMD pain
will be randomized to either an intervention arm or a placebo control group. Women in the
intervention arm will receive 8 weeks of progressive exercise MCTF of the cervical muscles,
twice per week. Women in the placebo arm will receive innocuous transcutaneous electrical
nerve stimulation (turn off). Our primary outcomes will be changes in 1) pain, measured with
the Visual Analogue Scale, 2) brain structure and networks, measured by fractional anisotropy
(brain structure) and the blood-oxygen-level dependent signal (brain networks). Outcomes will
be measured at baseline, after 8 weeks of treatment, and 4 months after treatment ends.
Results will directly inform and guide clinicians in prescribing more effective interventions
for women with TMD
Description:
To treat musculoskeletal disorders, looking at the brain is an unusual strategy but one with
high potential for effectiveness. Exercise can potentially train the brain if we understand
the links between exercise and productive changes in the brain. Given the high prevalence,
impact, and burden of musculoskeletal disorders (MSKDs), therapies need to focus on the
origin of the problem to be more effective and reduce economic costs. The latest evidence
highlights the need for musculoskeletal rehabilitative therapy, including exercise, to look
both at local structural and functional abnormalities of the MSK system and at alterations
within the central nervous system. These central alterations have been shown to have a
crucial role in the pathophysiology and clinical manifestations of MSKDs. People with chronic
MSKDs show brain alterations such as decreased regional grey matter volume in brain areas
such as the cingulate cortex, the insula, and the superior frontal and temporal gyrus. They
also have impairments in pathways related to pain modulation. These brain alterations are
visible in people with chronic MSKDs such as low back pain, osteoarthritis, headaches, and
chronic temporomandibular disorders (TMDs).
Therapeutic exercise is a cornerstone for MSKD rehabilitation. Although its effects on pain
are not fully understood, therapeutic exercise is widely applied in a variety of painful MSK
conditions, including TMDs. Maladaptive changes in the motor cortex in MSKDs can improve
after specific exercise training through motor control exercises and skilled cognitive
practice, through strength and resistance training, and through novel motor training and
visual feedback. However, all this evidence comes from preliminary studies with small sample
sizes, before-and-after designs, and in specific clinical populations. Expanding this
knowledge base to other clinical populations, with stronger study designs such as randomized
controlled trials (RCTs), is important to accurately understand the effects of exercise
therapy on brain plasticity and determine whether this approach is effective to manage MSKDs.
Our team is interested in managing TMDs through exercise therapy. From our previous studies
on neck muscle impairment in people with TMDs and our recent update of a systematic review on
therapeutic exercise to manage TMDs, we conclude that motor control exercise is a promising
option to treat people with TMDs. However, the evidence is still limited and more
high-quality investigations on the effectiveness of novel motor training in TMDs is needed.
OBJECTIVES
1. Determine the impact of motor control training using visual feedback (MCTF) on
pain-disability related outcomes such as pain intensity, pain pressure thresholds and
jaw disability. We will compare outcomes for people with TMDs who receive MCTF or a
placebo treatment after 8 weeks of treatment, and 4 months after treatment ends.
2. Assess the impact of MCTF and explore its mechanisms of action on brain structure using
DTI.
3. Assess the impact of MCTF on brain networks using rsfMRI.
4. Determine the effectiveness of MCTF in people with TMDs to restore normal muscular
structure, performance and fatigability of the cervical muscles when compared with a
placebo group.
THE PROPOSED TRIAL: MATERIALS AND METHODS Design: This study will be a randomized controlled
trial (RCT). A randomization sequence will be computer-generated by a research assistant (RA)
not involved in the study. To ensure concealment, the RA will distribute the results of the
sequence to the therapist in consecutively numbered, opaque, and sealed envelopes.
Participants will be unaware of the study hypothesis. Assessors (who will measure
clinician-assessed tests and analyze imaging outcomes) and the statistician will be blinded
to the hypothesis and group allocation, following established guidelines. Participants
randomized to the treatment group will receive MCTF as described in the Intervention section.
Participants randomized to the placebo group will receive placebo transcutaneous electrical
nerve stimulation (TENS) as described in the Intervention section.
Participants: A convenience sample of people who attend the TMD/Orofacial Pain clinic (School
of Dentistry, Faculty of Medicine & Dentistry, University of Alberta (UofA)) will be
recruited.
Sample Size: This will be a pilot study. Based on data of previous study, using pain
intensity as a main outcome and the ANOVA repeated measures within-between interaction
(effect size d=0.27) using α=0.05 and β=0.95, a sample size of approximately 18 subjects per
each group is required. Due to the possibility of a 10% of dropouts, we will recruit 20
subjects per group. Sample size calculation for the MRI variables was based on values of FA
measurements of White Matter (WM) obtained from the WM adjacent to S1/M1 area obtained from
Moayedi et al study on subjects with TMD. Based on a moderate difference between groups
(effect size d=0.7) using α=0.05 and β=0.20, using an ANOVA analysis for 2 groups, a sample
size of approximately 10 subjects per each group is required
PROCEDURES General Considerations: An experienced assessor will determine eligibility of
participants and will evaluate them with the standardized forms from the new DC/TMD. REDcap,
a password protected web platform (supported by the UofA) will be used to collect all
outcomes.
Twenty subjects (10 subjects from the exercise group and 10 subjects from the placebo group)
will be randomly allocated to undergo magnetic resonance imaging assessments of their brains
at baseline, 2, and 6 months after randomization for both groups (treatment and control
groups) if budget permits.
Primary Outcome Variables: The main outcome measures for this study are pain intensity
(measured by the VAS) and Fractional Anisotropy (FA) and functional brain networks (evaluated
by imaging).
All MRI will be performed in the Peter S. Allen MR Imaging Centre at the UofA by a certified
MRI technologist.
Secondary Outcomes: will be discussed in the section of outcomes. The following will be
considered secondary outcomes: The Neck Disability Index, Jaw function, Pressure pain
threshold (PPT), cervical flexor muscle performance, Neck Extensor Endurance Test (NEET), the
Neck Flexor Endurance test (NFET), Neck muscle structure, and Global Rating Scale (GRS)
INTERVENTION Early evidence from our research has shown that participants with TMDs present
with abnormalities of the cervical flexor and extensor muscles. Exercises targeting these
impairments reduce pain and level of dysfunction in people with cervical involvement. Thus,
cervical motor control exercises are one of the most promising choices to treat people with
TMDs. Treatment will consist of an 8-week progressive program of neck flexor and extensor
exercises, performed for 30-45 min twice a week.
Neck flexor training: Exercise during the first stage will be an incremental craniocervical
flexion movement in a relaxed, supine lying position. This exercise targets the deep flexors
of the upper cervical region, the longus capitis and colli, rather than the superficial
flexors, the sternocleidomastoid and anterior scalene muscles. Participants will be
instructed to perform and hold progressively inner range positions of craniocervical flexion,
using a pressure biofeedback connected to a screen. This will maximize feedback to the
participants as described in Armijo-Olivo et al. Once the correct craniocervical flexion
motion is achieved, participants will begin to hold progressively increasing ranges of
craniocervical flexion. They will use feedback from the pressure unit placed behind their
neck for 5 pressure targets (from 20 mmHg to 30 mmHg). Participants will be asked to hold
each level for 10 s and perform 10 repetitions without compensatory movements, with brief
rest periods between each contraction (~3-5 s). In the last 2 weeks of the exercise program,
participants will perform higher-load exercise with head weight as the load. Numbers of
repetitions and sets will be increased as permitted by the participant's response to the
exercise. An endurance element will be incorporated by increasing the time the position is
held, depending on the participant's progress.
Neck extensor training: Initially, participants will perform craniocervical extension and
upper cervical rotation in a prone on elbows position while maintaining the cervical spine in
a neutral position. They will progress to a 4-pt kneeling position. These exercises are
designed to target the sub-occipital muscles. Attention will first be given to the spinal and
scapular postures in the prone on elbows or 4-pt kneeling position. In the second phase of
the exercise program, participants will perform higher-load exercise with head weight as the
load, focusing on training the deep cervical extensors (the semispinalis cervicis/multifidus
group). In this stage, they will initially perform up to 15 repetitions of neck extension
while maintaining their head in a neutral position during 4-pt kneeling. Numbers of
repetitions and sets will be increased as permitted by the participant's response to the
exercise. An endurance element will be incorporated by increasing the time the position is
held, depending on the participant's progress.
Participants will be asked to refrain from seeking any additional treatment during the study
and will be asked to register their compliance with the exercise program in a daily diary
using REDCap.
Placebo: The placebo group will receive placebo TENS (switched-off TENS apparatus with no
perceptible stimulation). Four electrodes, 50 x 35 mm, will be placed on the neck muscles.
The participant will be informed that this therapy is called a "subthreshold current" and
they might not be able to feel any sensation underneath the electrodes during the treatment.
The placebo treatment will be for 30 min twice a week for 8 weeks, as for the intervention
group.
STATISTICAL ANALYSIS The analysis will follow the intention to treat principle. We will test
for significant differences in VAS, PPT, TMDs and neck disabilities at baseline, after 8
weeks of treatment, and 4 months after treatment ends (6 months) between participants
receiving MCTF and a placebo group. A two-way mixed ANOVA with repeated measures will be used
for each outcome (Objective 1); We will test for significant changes in FA at baseline, after
8 weeks of treatment, and 4 months after treatment ends (6 months) between participants
receiving MCTF and a placebo group, using a two-way mixed ANOVA with repeated measures. To
determine the relationship between FA and the pain-disability and psychological outcomes, a
multiple regression analysis will be conducted (Objective 2); We will determine if there are
significant changes in rsfMRI networks after 8 weeks of treatment, and 4 months after
treatment ends (6 months) between individuals receiving MCTF and a placebo group, using a
two-way mixed ANOVA with repeated measures for each outcome. To determine the relationship
between rsfMRI and the pain-disability and psychological outcomes, a multiple regression
analysis will be conducted (Objective 3); We will determine if there are significant changes
in CCFT, NEET, and NEFT, and cervical muscle structure at baseline, after 8 weeks of
treatment, and 4 months after treatment ends (6 months) between individuals receiving MCTF
and a placebo group, using a two-way mixed ANOVA with repeated measures for each outcome
(Objective 4).
Psychological functioning variables (distress, depression, anxiety) will be covariates. The
alpha level will be set at α = 0.05. A Bonferroni adjusted p-value will be applied to correct
for potential multiple comparisons and a Bonferroni post hoc test will be used to determine
the significant difference between pairwise comparisons. Effect sizes and minimal important
difference of the outcomes (using the GRS as an anchor measure) will be used to determine the
clinical significance of results.